ABSTRACT The benefits of adolescent vaccines are well known for preventing meningococcal infection and human papillomavirus (HPV)-related cancers. Yet, many adolescents in the United States (US) remain under- vaccinated, with vaccination rates among rural adolescents significantly lower than among their urban peers. Of all recommended adolescent vaccines, the urban-rural disparity is exceptionally stark for coverage of HPV vaccine, particularly in Southern states like North and South Carolina, which currently fall far below the Healthy People 2020 goal of ?80% coverage. Barriers to vaccine uptake among rural youth identified in the literature include a paucity of pediatric primary care providers in rural areas, financial barriers to vaccinations, and negative parental attitudes towards vaccines. Our multidisciplinary team of investigators from Duke University and the University of South Carolina, in partnership with the state health departments from North and South Carolina, proposes to examine barriers to HPV vaccination reported by parents of adolescents in the rural South and then use these findings to tailor the Keen on Teen Vaccines intervention previously implemented by our team in rural North Carolina. The tailored intervention will address vaccination barriers reported by parents of adolescents in rural communities across the Southern US. The intervention will be adapted for dissemination via public schools, with the core intervention component consisting of educational modules on adolescent vaccines, delivered in- person by school nurses to parents of adolescents ages 10-11, followed by reminders to promote vaccine uptake. A quantitative survey in 8 Southern states and qualitative data from stakeholders and parents in rural and urban counties in North and South Carolina will identify differences in barriers to vaccination between rural and urban parents and inform the adaptation of the intervention; feasibility and initial efficacy will be evaluated in a controlled before-after trial. The central hypothesis is that the adapted Keen on Teen Vaccines intervention will improve rates of HPV vaccination among rural adolescents. The specific aims are to (1) Examine barriers to adolescent vaccinations reported by rural versus urban parents in order to inform the tailoring of the Keen on Teen Vaccines intervention for rural communities in the US South, (2) Tailor the Keen on Teen Vaccines intervention to address rural parents' perceived barriers to vaccination, adapt the intervention for dissemination in school settings in rural North and South Carolina, and assess its acceptability with key stakeholders, and (3) Evaluate feasibility and preliminary efficacy of the adapted intervention for increasing vaccine uptake among adolescents in rural North and South Carolina. If successful, this project will significantly improve our understanding of urban-rural vaccination disparities and yield an innovative, tailored intervention to increase vaccination coverage, particularly of the HPV vaccine, among rural adolescents. The study will describe the acceptability, feasibility, and initial efficacy of the adapted Keen on Teen Vaccines intervention and inform future efforts to scale up the intervention to rural counties across the Southern US.